Dissecting the assembly pathway of the 20S proteasome

AbstractProteasomes reach their mature active state via a complex cascade of folding, assembly and processing events. The Rhodococcus proteasome offers a means to dissect the assembly pathway and to characterize intermediates; its four subunits (α1, α2, β1, β2) assemble efficiently in vitro with any combination of α and β. Assembly studies with wild-type and N-terminally truncated β-subunits in conjunction with refolding studies allowed to define the role of the propeptide which is two-fold: It supports the initial folding of the β-subunits and it promotes the maturation of the holoproteasomes

The proteasome: Paradigm of a self-compartmentalizing protease

and unfolding are closely related mechanistically, it is assumed, but not proven, that this task is performed by ATPase complexes, which bear some resemblance to the chaperonins and have been referred to as “reverse chaperones ” or “unfoldases ” (Lupas et al., 1993). Since their action requires the hydrolysis of ATP, protein degradation becomes energy-dependent, although the hydrolysis of the polypeptide chain itself is an exergonic process. Self-compartmentalizing proteases are common in all three domains of life: archaea, bacteria, and eukarya. This bears testimony to an old evolutionary principle. In fact, contrary to organelles such as the lysosome, self-compartmentalizing molecular devices offer far greater flexibility: when equipped with the appropriate localiza